PMID- 34244238
OWN - NLM
STAT- MEDLINE
DCOM- 20211221
LR  - 20240214
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 70
IP  - 10
DP  - 2021 Oct
TI  - Insulin Resistance in Skeletal Muscle Selectively Protects the Heart in Response 
      to Metabolic Stress.
PG  - 2333-2343
LID - 10.2337/db20-1212 [doi]
AB  - Obesity and type 2 diabetes mellitus (T2DM) are the leading causes of 
      cardiovascular morbidity and mortality. Although insulin resistance is believed 
      to underlie these disorders, anecdotal evidence contradicts this common belief. 
      Accordingly, obese patients with cardiovascular disease have better prognoses 
      relative to leaner patients with the same diagnoses, whereas treatment of T2DM 
      patients with thiazolidinedione, one of the popular insulin-sensitizer drugs, 
      significantly increases the risk of heart failure. Using mice with skeletal 
      musclespecific ablation of the insulin receptor gene (MIRKO), we addressed this 
      paradox by demonstrating that insulin signaling in skeletal muscles specifically 
      mediated cross talk with the heart, but not other metabolic tissues, to prevent 
      cardiac dysfunction in response to metabolic stress. Despite severe 
      hyperinsulinemia and aggregating obesity, MIRKO mice were protected from 
      myocardial insulin resistance, mitochondrial dysfunction, and metabolic 
      reprogramming in response to diet-induced obesity. Consequently, the MIRKO mice 
      were also protected from myocardial inflammation, cardiomyopathy, and left 
      ventricle dysfunction. Together, our findings suggest that insulin resistance in 
      skeletal muscle functions as a double-edged sword in metabolic diseases.
CI  - (c) 2021 by the American Diabetes Association.
FAU - Jia, Dandan
AU  - Jia D
AD  - Institute of Sports and Exercise Biology, School of Physical Education, Shaanxi 
      Normal University, Xi'an, Shaanxi, China.
AD  - Department of Pharmacology, Barshop Institute for Longevity and Aging Studies, 
      University of Texas Health Science Center at San Antonio, San Antonio, TX.
FAU - Zhang, Jun
AU  - Zhang J
AD  - Department of Pharmacology, Barshop Institute for Longevity and Aging Studies, 
      University of Texas Health Science Center at San Antonio, San Antonio, TX.
FAU - Liu, Xueling
AU  - Liu X
AD  - Department of Pharmacology, Barshop Institute for Longevity and Aging Studies, 
      University of Texas Health Science Center at San Antonio, San Antonio, TX.
FAU - Andersen, John-Paul
AU  - Andersen JP
AD  - Department of Pharmacology, Barshop Institute for Longevity and Aging Studies, 
      University of Texas Health Science Center at San Antonio, San Antonio, TX.
FAU - Tian, Zhenjun
AU  - Tian Z
AD  - Institute of Sports and Exercise Biology, School of Physical Education, Shaanxi 
      Normal University, Xi'an, Shaanxi, China.
FAU - Nie, Jia
AU  - Nie J
AD  - Department of Pharmacology, Barshop Institute for Longevity and Aging Studies, 
      University of Texas Health Science Center at San Antonio, San Antonio, TX.
FAU - Shi, Yuguang
AU  - Shi Y
AUID- ORCID: 0000-0002-9979-5661
AD  - Department of Pharmacology, Barshop Institute for Longevity and Aging Studies, 
      University of Texas Health Science Center at San Antonio, San Antonio, TX 
      shiy4@uthscsa.edu.
LA  - eng
SI  - figshare/10.2337/figshare.14903118
GR  - P30 CA054174/CA/NCI NIH HHS/United States
GR  - R01 AG055747/AG/NIA NIH HHS/United States
GR  - S10 OD021805/OD/NIH HHS/United States
GR  - T32 GM108563/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20210708
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Insulin)
RN  - EC 2.7.10.1 (Receptor, Insulin)
SB  - IM
MH  - Animals
MH  - Cytoprotection/genetics
MH  - Diet, High-Fat
MH  - Glucose Intolerance/genetics/metabolism/pathology
MH  - Heart/physiology
MH  - Heart Diseases/genetics/metabolism/pathology/*prevention & control
MH  - Hyperinsulinism/genetics/metabolism/pathology
MH  - Insulin/metabolism
MH  - Insulin Resistance/genetics/*physiology
MH  - Male
MH  - Metabolic Diseases/genetics/metabolism/pathology/physiopathology
MH  - Mice
MH  - Mice, Knockout
MH  - Muscle, Skeletal/*metabolism
MH  - Myocardium/*metabolism/pathology
MH  - Obesity/etiology/metabolism/physiopathology
MH  - Organ Specificity/genetics
MH  - Receptor, Insulin/genetics/metabolism
MH  - Signal Transduction/genetics
MH  - Stress, Physiological/genetics/*physiology
PMC - PMC8576508
EDAT- 2021/07/11 06:00
MHDA- 2021/12/22 06:00
PMCR- 2022/10/01
CRDT- 2021/07/10 05:40
PHST- 2020/11/30 00:00 [received]
PHST- 2021/07/02 00:00 [accepted]
PHST- 2021/07/11 06:00 [pubmed]
PHST- 2021/12/22 06:00 [medline]
PHST- 2021/07/10 05:40 [entrez]
PHST- 2022/10/01 00:00 [pmc-release]
AID - db20-1212 [pii]
AID - 201212 [pii]
AID - 10.2337/db20-1212 [doi]
PST - ppublish
SO  - Diabetes. 2021 Oct;70(10):2333-2343. doi: 10.2337/db20-1212. Epub 2021 Jul 8.